Toluene → Flometoquin

HRID 2273841Notes

Reaction equation

HRID 2273841 reaction equation
C1(C)C=CC=CC=1.[CH2:8]([C:10]1[NH:11][C:12]2[C:17]([C:18](=[O:21])[C:19]=1[CH3:20])=[CH:16][C:15]([O:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=1)=[C:14]([CH3:34])[CH:13]=2)[CH3:9].[OH-].[Na+].Cl[C:38]([O:40][CH3:41])=[O:39]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.CC(N(C)C)=O>[C:38](=[O:39])([O:40][CH3:41])[O:21][C:18]1[C:17]2[C:12](=[CH:13][C:14]([CH3:34])=[C:15]([O:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][C:30]([F:31])([F:32])[F:33])=[CH:25][CH:24]=3)[CH:16]=2)[N:11]=[C:10]([CH2:8][CH3:9])[C:19]=1[CH3:20]

Participants

8

Reactant 4

HCID 1140TolueneHCID 6586Methyl chloroformateHCID 14798Sodium HydroxideHCID 67119408HCID 67119408, compound

Product 1

HCID 67119441FlometoquinYield 98%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

Toluene (810 ml), 90 ml of dimethyl acetamide, 113.2 g of 2-ethyl-3,7-dimethyl-6-(4-(trifluoromethoxy)phenoxy)quinolin-4(1H)-one, and 4.8 g of tetrabutylammonium bromide were added to a glass vessel equipped with a stirring device, a thermometer, and a reflux condenser and having a volume of 3000 ml, and the mixture was stirred at room temperature. A 48% aqueous sodium hydroxide solution (50 g) was added dropwise thereto at 30 to 35° C., and the mixture was stirred at the same temperature for one hr. After cooling to 10 to 15° C., 34 g of methyl chloroformate was added dropwise, and a reaction was allowed to proceed at the same temperature for one hr. Water was added to the reaction solution. After washing, toluene was removed by evaporation, and the precipitated solid was collected by a suction filter. The solid was dried in vacuo to give 2-ethyl-3,7-dimethyl-6-(4-(trifluoromethoxy)phenoxy)quinolin-4-yl methyl carbonate (128 g, yield 98%). It was confirmed from the results of measurement of 1H-NMR that the compound thus obtained was a compound of No. 120 described in WO2006/013896 (patent document 1).

Workup

  1. customequipped with a stirring device
  2. stirringat 30 to 35° C., and the mixture was stirred at the same temperature for one hr
  3. temperatureAfter cooling to 10 to 15° C.
  4. washAfter washing
  5. customtoluene was removed by evaporation
  6. customthe precipitated solid was collected by a suction
  7. filtrationfilter
  8. customThe solid was dried in vacuo

Sources & evidence

ORD record
ord-420f33d954cd40b28f13a7a35c8de5f5
Source dataset
uspto-grants-2015_09
Patent number
US09126934B2

Reaction notes

Loading…